DESCRIPTION: State the application's broad, long-term objectives and specific aims, making referenceTWhe health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. This application will aid the development of the largest islet-cell isolation and distribution center in the nation. Tto present RFA catalyzed the unification of multiple key resources to establish this endeavor. Contributors to this effort include: 1) An islet isolation and transplantation laboratory with nearly 10 years experience in islet-sharing progra (UCLA-VA Medical Center); 2) The largest academic Good Manufacturing Processing (GMP) facility in the Unitei States, located at City of Hope (COH) National Medical Center, an institution with a long history in diabetes research, cell biology research, and bone marrow transplantation research (immunosuppressive regimens), conveniently situated i a geographic area with a population of more than 17 million in the immediate vicinity and approximately 33 millio: statewide, with excellent air transportation to surrounding states; 3) An agreement for a consortium between six loca General Clinical Research Centers (GCRCs) and satellites to conduct islet cell transplantation and characterization oi metabolic processes in patients transplanted at up to 14 transplant centers; 4) A major organ harvesting organization (SCOPC) with the potential of procuring 350pancreata annually, and over 600 pancreata upon successful collaboration with other statewide organ procurement organizations (OPOs); and, 5) The existence of many statewide academic institutions with ongoing islet-cell research that can benefit from the Southern California Islet-Cell Resources (SC-ICR Center. With these outstanding resources, the SC-ICR is committed to establish the following: 1) Isolation anc distribution of up to 75 pancreata in the first year and more than 200 pancreata by year 4; 2) Technologic advancement of islet-cell proliferation and cryopreservation techniques to allow for multiple donor use or repeated islet transfer from stored or proliferated cells; 3) Technologic advancement of islet isolation to improve yield and functionality; 4 Interaction with local OPOs and the United Network for Organ Sharing (UNOS) to develop new organ allocation policies and reduce/eliminate the inequitable distribution of "clinical grade" pancreata for whole organ versus islet transplantation; and, 5) Development of investigative methods for predicting potential graft rejection and new immum tolerance strategies to reduce dependency on immunosuppressive regimens. Thus, the inception of the SC-ICR will b instrumental in advancing the field of islet-cell physiology and therapeutic use. Through this effort, the dream o conquering Type 1 diabetes mellitus and will be closer to realization. PERFORMANCE SITE(S) (organization, city, state) . Beckman Research Institute City of Hope Duarte, CA KEY PERSONNEL. See instructions on Page Name Arthur Riggs, Ph.D. Fouad Kandeel, M.D., Ph.D. Craig Smith, M.D. Linda Shevlin David Ikle, Ph.D. Ivan Todorov, Ph.D. Yoko Mullen, M.D., Ph.D. David DiGiusto, Ph.D. Tom Balon, Ph.D. Howard Marx, M.D. Pinchas Cohen, M.D. Robert Ferry, Jr., M.D. Rama Natarajan, Ph.D. David Bleich, M.D. Eli Ipp, M.D. 11. Use continuation pages as neededto provide the required information in the format shown below. .Organization Role on Project City of Hope Principal Investigator City of Hope Co-Principal Investigator UCLA/City of Hope Co-Principal Investigator UCLA/City of Hope Center Coordinator City of Hope Director of Registry UCLA/City of Hope Director of Islet Isolation UCLA / City of Hope Director of Quality Control City of Hope Co-Director of Quality Control (GMP) City of Hope Co-Director of Quality Control City of Hope Co-Investigator of Invasive Radiology UCLA Project Lead Investigator UCLA Project Lead Investigator City of Hope Project Lead Investigator City of Hope Co-Director of Developmental Research Harbor-UCLA Co-Director of Developmental Research PHS 398 (Rev. 4/98) Page 2 BB Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.